The science of analytical chemistry has, and continues to make progress. The field involves the ability to assay sample materials to determine if a particular substance or substances is present, and if so, the amount of that substance. Frequently, the term “analyte” is used to describe the substance being tested. This term will be used hereafter.
Early examples of the application of analytical chemistry include litmus paper, which changes color in response to acid or base concentration as well as devices such as those incorporating test papers measuring urinary protein. To say that the field has become more sophisticated since then is an understatement.
One area of importance in analytical chemistry is the testing and evaluation of liquid samples. “Liquid sample” as used hereafter refers to materials such as blood, urine and, more particularly for this disclosure, water.
It is desirable and necessary to analyze water for various components. For example, it may be important to determine if a water sample is potable. Further, water samples are used for different purposes. Depending upon the use to which the sample is to be put, one or more parameters, such as pH, total alkalinity, calcium hardness, total hardness, and amount of particular analytes such as total chlorine, free chlorine, combined chlorine, sodium content, etc., may be important. For example, when the water sample is taken from a swimming pool, either or both of combined chlorine and free chlorine may be important. Where the water is to be used for an industrial cooling system, total alkalinity or total hardness may be important. When the water is to be used in the health profession, any number of analytes may be of interest and important. These are some examples of the type of uses for water samples. The skilled artisan will be familiar with many others, which need not be set forth here. Further, the literature on analysis of liquid samples other than water is vast.
Analysis of water samples can be accomplished with any number of different systems. Generally, however, these systems can be divided into “dry chemistry” and “wet chemistry” systems.
In a wet chemistry system, essentially one adds either a liquid testing agent or a dissolvable testing agent to a liquid sample. The testing agent reacts with the analyte of interest, leading to formation of a detectable signal. Preferably, this is the formation of a visible “marker,” such as a color or change in color. Again, the artisan will be familiar with other systems such as measurement of light absorption photometers, etc. For purposes of this disclosure, however, the discussion will focus on visible formation and changes in color, rather than systems such as light photometers solely to facilitate understanding.
In these wet chemistry systems, the reacted liquid sample is then compared to some reference standard. Generally, this takes the form of a coded reference linking concentration of the analyte to a particular color or degree of color. A low concentration may be indicated by a very pale pink color, and a high concentration by one which is dark red, and vice versa.
Dry chemistry systems can be used to analyze many of the types of samples that wet chemistry systems are used to analyze. In these dry chemistry systems an apparatus, such as an absorbent pad or a test strip is impregnated with the test system discussed herein. The apparatus is contacted with the liquid sample, removed from it, and signal is “read” by means of the color formed, a coded reference, etc. As with wet chemistry systems, the signal that is generated is linked to a specific amount and/or concentration of an analyte under consideration.
The prior art literature on analytical chemistry is vast. For example, U.S. Pat. No. 4,811,254, to Wu, teaches reagent systems which can be used to detect total available chlorine over a range of from 0 to 5000 ppm. The reagents can be incorporated into a carrier matrix, such as filter paper, to produce a dry chemistry test strip useful in measuring total available chlorine. U.S. Pat. No. 5,710,372, to Becket, teaches test strips which include a plurality of test regions. Each region contains a different amount of a reagent system which reacts with an analyte of interest. A visual display results which permits the user to determine the amount of the analyte in the sample being analyzed. U.S. Pat. No. 5,620,658, to Jaunakais, teaches multicomponent test strips which contain reagents capable of converting undetectable analytes into detectable ones, via ionic change. U.S. Pat. No. 5,529,751, to Gargas, teaches a pH adjustment kit. Once the pH of the sample has been determined, a first reagent is added until the sample indicates that a proper pH has been obtained. The number of drops of the first reagent is then converted to a quantity of a second reagent, which is then used to modify pH of the source of the sample. U.S. Pat. No. 5,491,094, to Ramana, et al., teaches dry reagent test strips for determining free chlorine, using TMB derivatives. U.S. Pat. No. 4,904,605, to O'Brien, et al., teaches test strips which can be used to determine a plurality of different reagents. A dipstick containing a plurality of reagent pads is contacted to sample, signal is formed, and then compared to a reference standard. U.S. Pat. No. 4,481,296, to Halley, teaches compositions that are useful in determining the pH of a halogen containing solution.
The various forms of analytical test strips can be seen via review of, e.g., U.S. Pat. Nos. 5,962,339 and 5,302,346, to Midgley et al and Vogel et al, respectively, who incorporate movable particles into the test strips. U.S. Pat. No. 5,271,895 to McCroskey and U.S. Pat. No. 5,169,787 to Knappe utilize apparatus which separate materials from sample, while U.S. Pat. No. 6,159,747 to Harttig et al teaches a blister device in the apparatus which, when broken, distributes reagent. Various specific types of assays are also described as being available in dry chemistry apparatus form. U.S. Pat. No. 5,874,944 to Kuo, U.S. Pat. No. 5,468,647 to Skold, and U.S. Pat. No. 5,824,268 to Bernstein are exemplary of immunoassays that can be performed on apparatus of the type described herein. U.S. Pat. No. 5,922,283 to Hsu et al; U.S. Pat. No. 5,709,837 to Mori et al, U.S. Pat. Nos. 6,027,692 and 5,695,494 to Gelen et al; U.S. Pat. No. 5,470,752 to Burd, U.S. Pat. No. 4,806,478 to Stahl and U.S. Pat. No. 4,966,855 to Deneke et al all discuss specific reagent systems which can be used in dry chemistry test strip form.
Regardless of the type of assay carried out, the test apparatus requires a matrix of some type to which analytical reagents and samples can be applied. Classically, filter paper or other types of paper are used; however, the art has demonstrated that various other materials have been used. Rothe, et al, U.S. Pat. No. 4,604,264, is exemplary of a class of test strips which incorporate reagent containing films. Other U.S. patents, such as U.S. Pat. Nos. 3,897,214 to Lange et al; 3,802,842, also to Lange, et al, and U.S. Pat. No. 4,042,335 to Element describe the use of fleece, felt, or floculent materials, e.g., flocks, in test devices.
The plethora of U.S. patents in this area, coupled with the diverse approaches taken to the construction of the devices exhibits constant attempts to improve the quality and diversity of the devices.
One major issue that faces the manufacturer of any test apparatus is the need to have a device available that provides clear, easy to read signals where the amount of analyte in a sample is very small. Generally, test strips of the type described herein contain reagents which, upon reaction with a particular analyte, generate an observable signal, such as a color. In test strips designed to measure the amount of an analyte present, such as a pH test strip, the signal must be one which provides a distinct color or color change over a range of values, such that the different values can be distinguished from each other easily. A pH test strip that gave the same color whether the pH of a sample was 6.0 or 8.0, e.g., is useless in many applications.
In order to be useful, a test strip used in this situation should be able to delineate between analyte values clearly, accurately, and distinctly.
Another problem with test strips that are used to analyze samples containing vanishingly small amounts of analyte is that the test strips, when contacted to a liquid sample, de facto add reagents to the sample. Such reagents frequently contain materials such as buffers, which impact the analyte of interest.
It has now been found, however, that one can improve the usefulness of test strips and analytical devices markedly if one employs, as the matrix, a material which contains, at a minimum, a void fraction or void volume of at least about 80%, more preferably at least about 85%, more preferably at least about 90%, even more preferably at least about 93%, and most preferably about 93-97%.
“Void volume” or “void fraction” as used herein, are terms known in the art. One way of determining percent void volume is to use the following formula:
  V  =            [                        t          -                      (                                          f                /                d                            +              m                        )                          t            ]        ×    100  where V is the void volume, t is felt volume, f is the dry weight of the felt, d is the density of the material, and m is felt moisture. Of course, if another material, such as fleece is used, the adjective “felt” will change. A written definition is provided by The Dictionary of Paper, (George Banta Company, Menasha, Wis., 1965), incorporated by reference, which defines void fraction as “the ratio of the volume occupied by voids or air spaces to the gross volume of a sheet of paper. It may also be expressed as” unity minus the solid fraction.” The definition, while provided for paper, is employed herein for all types of matrices used.
It has also been found that the usefulness of test strips and analytical devices improves markedly if one uses, as the test matrix, absorbent material which, when contacted to liquids, imbibes from about 6 to about 30 times its dry weight in liquid, more preferably from about 6 to about 20 times its dry weight, and even more preferably, from about 8 to about 17 times its dry weight in liquid. This value is referred to as “uptake ratio,” defined as the value obtained by dividing the weight of water imbibed by the material, by its dry weight. In one embodiment of the invention, the imbibing property referred to herein and the void volume property referred to supra are shared by the material used for the matrix.
The examples which follow are exemplary of the invention, but should not be seen as being limiting of the general convention as described herein.